Deep learning-based COVID-19 diagnosis using CT scans with laboratory and physiological parameters

The global economy has been dramatically impacted by COVID-19, which has spread to be a pandemic. COVID-19 virus affects the respiratory system, causing difficulty breathing in the patient. It is crucial to identify and treat infections as soon as possible. Traditional diagnostic reverse transcription-polymerase chain reaction (RT-PCR) methods require more time to find the infection. A high infection rate, slow laboratory analysis, and delayed test results caused the widespread and uncontrolled spread of the disease. This study aims to diagnose the COVID-19 epidemic by leveraging a modified convolutional neural network (CNN) to quickly and safely predict the disease's appearance from computed tomography (CT) scan images and a laboratory and physiological parameters dataset. A dataset representing 500 patients was used to train, test, and validate the CNN model with results in detecting COVID-19 having an accuracy, sensitivity, specificity, and F1-score of 99.33%, 99.09%, 99.52%, and 99.24%, respectively. These experimental results suggest that our strategy performs better than previously published approaches.

Long-Term Effects of Mountain Hiking vs. Forest Therapy on Physical and Mental Health of Couples: A Randomized Controlled Trial.

BACKGROUND: Lifelong physical activity is related to longer health span, which is reflected at an individual level, and is of substantial socioeconomic relevance. Sedentary lifestyles, on the other hand, pose an increasingly major public health problem. In addition, the COVID-19 pandemic had a negative impact on activity levels and well-being. Previous research indicates that contact with nature might improve exercise levels as well as well-being. METHODS: This randomized, controlled clinical trial (ANKER-study) investigated the effects of two types of nature-based therapies (forest therapy and mountain hiking) in couples (FTG: n = 23; HG: n = 22;) with a sedentary or inactive lifestyle on health-related quality of life, relationship quality and other psychological and physiological parameters. RESULTS: The results of this study displayed that healthy and highly functioning women and men with sedentary lifestyles mentally benefit from contact with nature (quality of life, satisfaction with life, mood, internal and external health-related control beliefs). The gender-specific effect on women is most visible in the physiological outcomes (hemopoietic system, aerobic capacity, skeletal muscle mass and hydration) of mountain hiking. Men and women showed small improvements in blood pressure as a result of the interventions. CONCLUSIONS: The ANKER-study provides a method for valid comparison of forest therapy interventions for the first time. Regarding the COVID-19 pandemic, the nature-based intervention presented could offer a multimodal contribution to maintaining a more active lifestyle, further contact with nature that affects peoples physical as well as mental health, and an improvement in social interaction.

A Multisensor System Embedded in a Computer Mouse for Occupational Stress Detection.

Occupational stress is a major challenge in modern societies, related with many health and economic implications. Its automatic detection in an office environment can be a key factor toward effective management, especially in the post-COVID era of changing working norms. The aim of this study is the design, development and validation of a multisensor system embedded in a computer mouse for the detection of office work stress. An experiment is described where photoplethysmography (PPG) and galvanic skin response (GSR) signals of 32 subjects were obtained during the execution of stress-inducing tasks that sought to simulate the stressors present in a computer-based office environment. Kalman and moving average filters were used to process the signals and appropriately formulated algorithms were applied to extract the features of pulse rate and skin conductance. The results found that the stressful periods of the experiment significantly increased the participants' reported stress levels while negatively affecting their cognitive performance. Statistical analysis showed that, in most cases, there was a highly significant statistical difference in the physiological parameters measured during the different periods of the experiment, without and with the presence of stressors. These results indicate that the proposed device can be part of an unobtrusive system for monitoring and detecting the stress levels of office workers.

Physiological Behavior of COVID-19 Patients Using Wearable System and Markov Chains

This study seeks to continuously monitor key physiological parameters in progression and development in people infected with the COVID-19 virus. This will be developed through a wearable system where physiological and some hemodynamic data will be obtained. Based on this data collection, Markov chains will be applied in order to establish the probability of change in the progression of the disease. That is, the probability of complications from this condition or improvement of the infected patient. For the development of this study, a data collection system based mainly on MEMS-type sensors will be used, as well as the use of stochastic simulations to verify the development of Markov chains. It is important to mention that this is a study in development that seeks the rapid application for the monitoring of patients with this condition. © 2021 IEEE.

A Pilot study for Depression Detection during COVID-19 using Stroop Test

The Corona virus disease 2019 (COVID-19) pandemic has caused substantial increase in distress among people all over the world. This work aims to study depression during the COVID-19 among the educational sector and to develop a novel stroop test based depression detection system by analyzing the response time (RT) for normal stroop test (ST) and emotional stroop test (EST). The data for this work is collected from 44 participants. It is found that 66% of the participants have depression. The analysis of RT for ST and EST before and after showing video stimulus, indicates that there is a significant difference in change of response time (dRT) for both normal and depressive cases. Further this feature along with the physiological parameters (PhyP) of the participants are given to support vector machine (SVM) and extreme gradient boost (XGBoost) classifier to develop depression detection systems. The XGBoost provides highest accuracy of 85.71% with PhyP + ST dRT data and an accuracy of 71.43% with PhyP + EST dRT data. Therefore, the proposed systems may serve as a screening tool for depression during this pandemic situation. © 2021 IEEE

Comparison of Anthropometric and Physiological Profiles of Hungarian Female Rowers across Age Categories, Rankings, and Stages of Sports Career

There is very little research on the anthropometric and physiological profiles of lower-ranked young female athletes, even though, in most rowing clubs, such rowers constitute the vast majority. Therefore, this study investigated the anthropometric and physiological profiles of young Hungarian female rowers of different age categories and sports rankings (international vs. club). Anthropometric and physiological profiles were created for 36 junior (15–16 years), 26 older-junior (17–18 years), and 8 senior (19–21 years) female rowers who were club and international ranked members of seven of the largest Hungarian rowing clubs. Rowers >17-years-old with international rankings significantly outperformed their age-group peers with club rankings in terms of power, absolute VO2 max, and time to cover 2000 m, among other differences, but such differences were not observed with junior rowers. In all age groups, the length of the athletes’ sports career was not significantly associated with differences in anthropometric and physiological characteristics. This study suggests that ranking is not associated with differences in the anthropometric and physiological characteristics of juniors. Thus, with non-elite juniors, it can be more difficult to predict competition outcomes based on differences in anthropometric and physiological profiles.

CheckING: An IoT Device for COVID-19 Monitoring and Prevention

The COVID-19 pandemic has spread rapidly around the world forcing people to isolate at home and collapsing hospitals causing millions of deaths. The continuous and efficient monitoring of those who showed symptoms jointly with the analysis of the environment conditions to avoid the spread of the virus gave rise to the development of different technological alternatives. In the present work, a comprehensive device with multi-parameter sensing has been designed, emphasizing the integration of physiological and environmental parameters with remote monitoring, of the interest in the current pandemic context. © 2021 IEEE.

Comparison of Effects of N95 Respirators and Surgical Masks to Physiological and Psychological Health among Healthcare Workers: A Randomized Controlled Trial.

Since the onset of the coronavirus disease 2019 pandemic, wearing facemasks has become more important for healthcare workers. This study aimed to investigate and compare the influence of wearing N95 respirators and surgical masks for 8 h on physiological and psychological health. Sixty-eight healthcare workers were randomly assigned to the N95 respirator or surgical mask groups. Physiological parameters of participants were measured by Tensor Tip MTX at baseline and at the 2nd, 4th, 6th and 8th h of wearing the facemasks. The symptoms after wearing facemasks were also determined via the questionnaire. There were no significant changes in physiological parameters at most time checkpoints in both groups. Significant differences were observed in terms of heart rate at the 8th h, time trends (adjusted difference of least squares means were -8.53 and -2.01), and interaction of time and mask type between the two groups (p-value for interaction was 0.0146). The values of these physiological parameters were within normal ranges. The N95 respirator group had significantly higher incidences of shortness of breath, headache, dizziness, difficulty talking and fatigue that spontaneously resolved. In conclusion, healthcare workers who wore either N95 respirators or surgical masks during an 8 h shift had no obvious harmful effects on physiological and psychological health. Additionally, the N95 respirator group did not show a higher risk than the surgical mask group.

Influence of cuff pressures of automatic sphygmomanometers on pulse oximetry measurements.

Information about blood arterial oxygen saturation (SpO2) is crucial in critical care settings or home health monitoring during the COVID-19 pandemic. Also, we need to identify the factors that affect the SpO2 measurement. In this paper, the effect of compression of the cuff during noninvasive blood pressure (NIBP) measurement on the SpO2 results was investigated. A custom-made system was used for simultaneous measurement of NIBP and SpO2. The study was conducted on 213 subjects aged between 21 and 93, with a systolic blood pressure of (94 to 194) mmHg, diastolic blood pressure of (52-98) mmHg, and 994 NIBP readings were used for the analysis. During the NIBP measurement, momentary changes in SpO2 can reach ±17% and are in most cases positive (mean 2.9%). The change was not correlated with sex, age, height, body weight, BMI, HR and blood pressure. The obtained results show that frequent NIBP measurements may lead to wrong conclusions about SpO2. In our study, pressure measurements mainly caused the increase of blood oxygenation level.

A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the Remote Early Detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: It is currently thought that most-but not all-individuals infected with SARS-CoV-2 develop symptoms, but the infectious period starts on average 2 days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before they have overt symptoms, wearable devices could potentially and significantly reduce the proportion of transmissions by pre-symptomatic individuals. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests [to determine if there are antibodies against the SARS-CoV-2 in the blood] or SARS-CoV-2 infection tests such as polymerase chain reaction [PCR] or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the following two algorithms to detect first time SARS-CoV-2 infection including early or asymptomatic infection: • The algorithm using Ava bracelet data when coupled with self-reported Daily Symptom Diary data (Wearable + Symptom Data Algo; experimental condition) • The algorithm using self-reported Daily Symptom Diary data alone (Symptom Only Algo; control condition) In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. TRIAL DESIGN: The trial is a randomized, single-blinded, two-period, two-sequence crossover trial. The study will start with an initial learning phase (maximum of 3 months), followed by period 1 (3 months) and period 2 (3 months). Subjects entering the study at the end of the recruitment period may directly start with period 1 and will not be part of the learning phase. Each subject will undergo the experimental condition (the Wearable + Symptom Data Algo) in either period 1 or period 2 and the control condition (Symptom Only Algo) in the other period. The order will be randomly assigned, resulting in subjects being allocated 1:1 to either sequence 1 (experimental condition first) or sequence 2 (control condition first). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. PARTICIPANTS: The trial will be conducted in the Netherlands. A target of 20,000 subjects will be enrolled. Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. This results in approximately 6500 normal-risk individuals and 3500 high-risk individuals per sequence. Subjects will be recruited from previously studied cohorts as well as via public campaigns and social media. All data for this study will be collected remotely through the Ava COVID-RED app, the Ava bracelet, surveys in the COVID-RED web portal and self-sampling serology and PCR kits. More information on the study can be found in www.covid-red.eu . During recruitment, subjects will be invited to visit the COVID-RED web portal. After successfully completing the enrolment questionnaire, meeting eligibility criteria and indicating interest in joining the study, subjects will receive the subject information sheet and informed consent form. Subjects can enrol in COVID-RED if they comply with the following inclusion and exclusion criteria: Inclusion criteria: • Resident of the Netherlands • At least 18 years old • Informed consent provided (electronic) • Willing to adhere to the study procedures described in the protocol • Must have a smartphone that runs at least Android 8.0 or iOS 13.0 operating systems and is active for the duration of the study (in the case of a change of mobile number, the study team should be notified) • Be able to read, understand and write Dutch Exclusion criteria: • Previous positive SARS-CoV-2 test result (confirmed either through PCR/antigen or antibody tests; self-reported) • Current suspected (e.g. waiting for test result) COVID-19 infection or symptoms of a COVID-19 infection (self-reported) • Participating in any other COVID-19 clinical drug, vaccine or medical device trial (self-reported) • Electronic implanted device (such as a pacemaker; self-reported) • Pregnant at the time of informed consent (self-reported) • Suffering from cholinergic urticaria (per the Ava bracelet's user manual; self-reported) • Staff involved in the management or conduct of this study INTERVENTION AND COMPARATOR: All subjects will be instructed to complete the Daily Symptom Diary in the Ava COVID-RED app daily, wear their Ava bracelet each night and synchronize it with the app each day for the entire period of study participation. Provided with wearable sensor and/or self-reported symptom data within the last 24 h, the Ava COVID-RED app's underlying algorithms will provide subjects with a real-time indicator of their overall health and well-being. Subjects will see one of three messages, notifying them that no seeming deviations in symptoms and/or physiological parameters have been detected; some changes in symptoms and/or physiological parameters have been detected and they should self-isolate; or alerting them that deviations in their symptoms and/or physiological parameters could be suggestive of a potential COVID-19 infection and to seek additional testing. We will assess the intraperson performance of the algorithms in the experimental condition (Wearable + Symptom Data Algo) and control conditions (Symptom Only Algo). Note that both algorithms will also instruct to seek testing when any SARS-CoV-2 symptoms are reported in line with those defined by the Dutch national institute for public health and the environment 'Rijksinstituut voor Volksgezondheid en Milieu' (RIVM) guidelines. MAIN OUTCOMES: The trial will evaluate the use and performance of the Ava COVID-RED app and Ava bracelet, which uses sensors to measure breathing rate, pulse rate, skin temperature and heart rate variability for the purpose of early and asymptomatic detection and monitoring of SARS-CoV-2 in general and high-risk populations. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests, PCR tests and/or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each of the following two algorithms to detect first-time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava bracelet data when coupled with the self-reported Daily Symptom Diary data and the algorithm using self-reported Daily Symptom Diary data alone. In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. The protocol contains an additional twenty secondary and exploratory objectives which address, among others, infection incidence rates, health resource utilization, symptoms reported by SARS-CoV-2-infected participants and the rate of breakthrough and asymptomatic SARS-CoV-2 infections among individuals vaccinated against COVID-19. PCR or antigen testing will occur when the subject receives a notification from the algorithm to seek additional testing. Subjects will be advised to get tested via the national testing programme and report the testing result in the Ava COVID-RED app and a survey. If they cannot obtain a test via the national testing programme, they will receive a nasal swab self-sampling kit at home, and the sample will be tested by PCR in a trial-affiliated laboratory. In addition, all subjects will be asked to take a capillary blood sample at home at baseline (between month 0 and 3.5 months after the start of subject recruitment), at the end of the learning phase (month 3; note that this sampling moment is skipped if a subject entered the study at the end of the recruitment period), period 1 (month 6) and period 2 (month 9). These samples will be used for SARS-CoV-2-specific antibody testing in a trial-affiliated laboratory, differentiating between antibodies resulting from a natural infection and antibodies resulting from COVID-19 vaccination (as vaccination will gradually be rolled out during the trial period). Baseline samples will only be analysed if the sample collected at the end of the learning phase is positive, or if the subject entered the study at the end of the recruitment period, and samples collected at the end of period 1 will only be analysed if the sample collected at the end of period 2 is positive. When subjects obtain a positive PCR/antigen or serology test result during the study, they will continue to be in the study but will be moved into a so-called COVID-positive mode in the Ava COVID-RED app. This means that they will no longer receive recommendations from the algorithms but can still contribute and track symptom and bracelet data. The primary analysis of the main objective will be executed using the data collected in period 2 (months 6 through 9). Within this period, serology tests (before and after period 2) and PCR/antigen tests (taken based on recommendations by the algorithms) will be used to determine if a subject was infected with SARS-CoV-2 or not. Within this same time period, it will be determined if the algorithms gave any recommendations for testing. The agreement between these quantities will be used to evaluate the performance of the algorithms and how these compare between the study conditions. RANDOMIZATION: All eligible subjects will be randomized using a stratified block randomization approach with an allocation ratio of 1:1 to one of two sequences (experimental condition followed by control condition or control condition followed by experimentalcondition). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence, resulting in approximately equal numbers of high-risk and normal-risk individuals between the sequences. BLINDING (MASKING): In this study, subjects will be blinded to the study condition and randomization sequence. Relevant study staff and the device manufacturer will be aware of the assigned sequence. The subject will wear the Ava bracelet and complete the Daily Symptom Diary in the Ava COVID-RED app for the full duration of the study, and they will not know if the feedback they receive about their potential infection status will only be based on the data they entered in the Daily Symptom Diary within the Ava COVID-RED app or based on both the data from the Daily Symptom Diary and the Ava bracelet. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 20,000 subjects will be recruited and randomized 1:1 to either sequence 1 (experimental condition followed by control condition) or sequence 2 (control condition followed by experimental condition), taking into account their risk level. This results in approximately 6500 normal-risk and 3500 high-risk individuals per sequence. TRIAL STATUS: Protocol version: 3.0, dated May 3, 2021. Start of recruitment: February 19, 2021. End of recruitment: June 3, 2021. End of follow-up (estimated): November 2021 TRIAL REGISTRATION: The Netherlands Trial Register on the 18th of February, 2021 with number NL9320 ( https://www.trialregister.nl/trial/9320 ) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

Development and Progress in Sensors and Technologies for Human Emotion Recognition.

With the advancement of human-computer interaction, robotics, and especially humanoid robots, there is an increasing trend for human-to-human communications over online platforms (e.g., zoom). This has become more significant in recent years due to the Covid-19 pandemic situation. The increased use of online platforms for communication signifies the need to build efficient and more interactive human emotion recognition systems. In a human emotion recognition system, the physiological signals of human beings are collected, analyzed, and processed with the help of dedicated learning techniques and algorithms. With the proliferation of emerging technologies, e.g., the Internet of Things (IoT), future Internet, and artificial intelligence, there is a high demand for building scalable, robust, efficient, and trustworthy human recognition systems. In this paper, we present the development and progress in sensors and technologies to detect human emotions. We review the state-of-the-art sensors used for human emotion recognition and different types of activity monitoring. We present the design challenges and provide practical references of such human emotion recognition systems in the real world. Finally, we discuss the current trends in applications and explore the future research directions to address issues, e.g., scalability, security, trust, privacy, transparency, and decentralization.

A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the remote early detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: It is currently thought that most-but not all-individuals infected with SARS-CoV-2 develop symptoms, but that the infectious period starts on average two days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before they have overt symptoms, wearable devices could potentially and significantly reduce the proportion of transmissions by pre-symptomatic individuals. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests [to determine if there are antibodies against the SARS-CoV-2 in the blood] or SARS-CoV-2 infection tests such as polymerase chain reaction [PCR] or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the following two algorithms to detect first time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava bracelet data when coupled with self-reported Daily Symptom Diary data (Wearable + Symptom Data Algo; experimental condition) the algorithm using self-reported Daily Symptom Diary data alone (Symptom Only Algo; control condition) In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. TRIAL DESIGN: The trial is a randomized, single-blinded, two-period, two-sequence crossover trial. All subjects will participate in an initial Learning Phase (varying from 2 weeks to 3 months depending on enrolment date), followed by two contiguous 3-month test phases, Period 1 and Period 2. Each subject will undergo the experimental condition (the Wearable + Symptom Data Algo) in one of these periods and the control condition (Symptom Only Algo) in the other period. The order will be randomly assigned, resulting in subjects being allocated 1:1 to either Sequence 1 (experimental condition first) or Sequence 2 (control condition first). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. PARTICIPANTS: The trial will be conducted in the Netherlands. A target of 20,000 subjects will be enrolled. Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence. This results in approximately 6,500 normal-risk individuals and 3,500 high-risk individuals per sequence. Subjects will be recruited from previously studied cohorts as well as via public campaigns and social media. All data for this study will be collected remotely through the Ava COVID-RED app, the Ava bracelet, surveys in the COVID-RED web portal, and self-sampling serology and PCR kits. During recruitment, subjects will be invited to visit the COVID-RED web portal ( www.covid-red.eu ). After successfully completing the enrolment questionnaire, meeting eligibility criteria and indicating interest in joining the study, subjects will receive the subject information sheet and informed consent form. Subjects can enrol in COVID-RED if they comply with the following inclusion and exclusion criteria. INCLUSION CRITERIA: Resident of the Netherlands At least 18 years old Informed consent provided (electronic) Willing to adhere to the study procedures described in the protocol Must have a smartphone that runs at least Android 8.0 or iOS 13.0 operating systems and is active for the duration of the study (in the case of a change of mobile number, study team should be notified) Be able to read, understand and write Dutch Exclusion criteria: Previous positive SARS-CoV-2 test result (confirmed either through PCR/antigen or antibody tests; self-reported) Previously received a vaccine developed specifically for COVID-19 or in possession of an appointment for vaccination in the near future (self-reported) Current suspected (e.g., waiting for test result) COVID-19 infection or symptoms of a COVID-19 infection (self-reported) Participating in any other COVID-19 clinical drug, vaccine, or medical device trial (self-reported) Electronic implanted device (such as a pacemaker; self-reported) Pregnant at time of informed consent (self-reported) Suffering from cholinergic urticaria (per the Ava bracelet's User Manual; self-reported) Staff involved in the management or conduct of this study INTERVENTION AND COMPARATOR: All subjects will be instructed to complete the Daily Symptom Diary in the Ava COVID-RED app daily, wear their Ava bracelet each night and synchronise it with the app each day for the entire period of study participation. Provided with wearable sensor and/or self-reported symptom data within the last 24 hours, the Ava COVID-RED app's underlying algorithms will provide subjects with a real-time indicator of their overall health and well-being. Subjects will see one of three messages, notifying them that: no seeming deviations in symptoms and/or physiological parameters have been detected; some changes in symptoms and/or physiological parameters have been detected and they should self-isolate; or alerting them that deviations in their symptoms and/or physiological parameters could be suggestive of a potential COVID-19 infection and to seek additional testing. We will assess intraperson performance of the algorithms in the experimental condition (Wearable + Symptom Data Algo) and control conditions (Symptom Only Algo). MAIN OUTCOMES: The trial will evaluate the use and performance of the Ava COVID-RED app and Ava bracelet, which uses sensors to measure breathing rate, pulse rate, skin temperature, and heart rate variability for the purpose of early and asymptomatic detection and monitoring of SARS-CoV-2 in general and high-risk populations. Using laboratory-confirmed SARS-CoV-2 infections (detected via serology tests, PCR tests and/or antigen tests) as the gold standard, we will determine the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each of the following two algorithms to detect first-time SARS-CoV-2 infection including early or asymptomatic infection: the algorithm using Ava Bracelet data when coupled with the self-reported Daily Symptom Diary data, and the algorithm using self-reported Daily Symptom Diary data alone. In addition, we will determine which of the two algorithms has superior performance characteristics for detecting SARS-CoV-2 infection including early or asymptomatic infection as confirmed by SARS-CoV-2 virus testing. The protocol contains an additional seventeen secondary outcomes which address infection incidence rates, health resource utilization, symptoms reported by SARS-CoV-2 infected participants, and the rate of breakthrough and asymptomatic SARS-CoV-2 infections among individuals vaccinated against COVID-19. PCR or antigen testing will occur when the subject receives a notification from the algorithm to seek additional testing. Subjects will be advised to get tested via the national testing programme, and report the testing result in the Ava COVID-RED app and a survey. If they cannot obtain a test via the national testing programme, they will receive a nasal swab self-sampling kit at home, and the sample will be tested by PCR in a trial-affiliated laboratory. In addition, all subjects will be asked to take a capillary blood sample at home at baseline (Month 0), and at the end of the Learning Phase (Month 3), Period 1 (Month 6) and Period 2 (Month 9). These samples will be used for SARS-CoV-2-specific antibody testing in a trial-affiliated laboratory, differentiating between antibodies resulting from a natural infection and antibodies resulting from COVID-19 vaccination (as vaccination will gradually be rolled out during the trial period). Baseline samples will only be analysed if the sample collected at the end of the Learning Phase is positive, and samples collected at the end of Period 1 will only be analysed if the sample collected at the end of Period 2 is positive. When subjects obtain a positive PCR/antigen or serology test result during the study, they will continue to be in the study but will be moved into a so-called "COVID-positive" mode in the Ava COVID-RED app. This means that they will no longer receive recommendations from the algorithms but can still contribute and track symptom and bracelet data. The primary analysis of the main objective will be executed using data collected in Period 2 (Month 6 through 9). Within this period, serology tests (before and after Period 2) and PCR/antigen tests (taken based on recommendations by the algorithms) will be used to determine if a subject was infected with SARS-CoV-2 or not. Within this same time period, it will be determined if the algorithms gave any recommendations for testing. The agreement between these quantities will be used to evaluate the performance of the algorithms and how these compare between the study conditions. RANDOMISATION: All eligible subjects will be randomized using a stratified block randomization approach with an allocation ratio of 1:1 to one of two sequences (experimental condition followed by control condition or control condition followed by experimental condition). Based on demographics, medical history and/or profession, each subject will be stratified at baseline into a high-risk and normal-risk group within each sequence, resulting in equal numbers of high-risk and normal-risk individuals between the sequences. BLINDING (MASKING): In this study, subjects will be blinded as to study condition and randomization sequence. Relevant study staff and the device manufacturer will be aware of the assigned sequence. The subject will wear the Ava bracelet and complete the Daily Symptom Diary in the Ava COVID-RED appfor the full duration of the study, and they will not know if the feedback they receive about their potential infection status will only be based on data they entered in the Daily Symptom Diary within the Ava COVID-RED app or based on both the data from the Daily Symptom Diary and the Ava bracelet. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): 20,000 subjects will be recruited and randomized 1:1 to either Sequence 1 (experimental condition followed by control condition) or Sequence 2 (control condition followed by experimental condition), taking into account their risk level. This results in approximately 6,500 normal-risk and 3,500 high-risk individuals per sequence. TRIAL STATUS: Protocol version: 1.2, dated January 22nd, 2021 Start of recruitment: February 22nd, 2021 End of recruitment (estimated): April 2021 End of follow-up (estimated): December 2021 TRIAL REGISTRATION: The trial has been registered at the Netherlands Trial Register on the 18th of February, 2021 with number NL9320 ( https://www.trialregister.nl/trial/9320 ) FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

A time-resolved proteomic and prognostic map of COVID-19.

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.